CH661922A5 - 6-DEOSSIANTRACICLINE. - Google Patents

Description

The invention relates to a process for the preparation of 6-deoxyanthracyclinones, and to some of the 6-deoxyanthraacyclinones.

The invention relates to a process for the preparation of 6-deoxyanthracyclinones having the general formula I

OH

OH

wherein R represents a hydrogen atom, a hydroxy group or a lower alkoxy group. The process which is illustrated in the following reaction scheme includes:

(i) acetylation of dimethyl 1,2,3,6-tetrahydro-phthalate (II) by treatment with acetic anhydride in the presence of tin tetrachloride followed by treatment with an acid or a weak base,

(ii) the reaction of the resulting dimethyl 1, 2,3,6-tetrahydro-4-ace-tylphthalate (III) with tosylhydrazine,

(iii) the reduction of the resulting dimethyl 1,1,3,6-tetrahydro-4 - (1-tosylhydrazono-ethyl) -phthalate (IV) with catechol borane and subsequently a rearrangement of the double bond from an endocyclic position to an exocyclic position in the presence of sodium acetate,

(iv) oxidation of the resulting 1,2-di- (methoxycarbonyl) -4 - ethylidene-cyclohexane (V) with potassium permanganate and treatment of the resulting a-hydroxy-ketone with ethylene glycol in the presence of a catalytic quantity of the acid p-toluenesulfonic,

(v) condensation of the resulting 2-methoxycarbonyl-5- [2-methyl-dioxolan-2-yl] -6-oxa-bicyclo [3,2, l] octane-7-one (VI) with a

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compound of the general formula VIII in which R has the aforementioned meaning (obtained by the action of an alkillithium on a compound of the general formula VII in which R has the aforementioned meaning),

(vi) opening of the lactone ring and elimination of the protective group of the keto group of the dioxolane in the resulting compound of formula IX in which R has a meaning defined above by methanolysis,

(vii) reduction of the keto groups of the resulting compound of general formula X wherein R has the above meaning by treatment with a pyridine-borane complex in the presence of trifluoracetic acid and conversion of the methoxycarbonyl group to a benzyloxycarbonyl group by treatment with fe-nildiazomethane,

(viii) esterification of the hydroxyl group and deesterification of the benzyloxycarbonyl group in the resulting compound of formula XI wherein R has the above meaning by treatment with acetic anhydride in pyridine in the presence of 4-dimethyl-

amino pyridine followed by heating to fall back with cyclohexene in the presence of a catalyst of palladium on coal,

(ix) cyclization of the resulting compound of the general formula XII wherein R 'represents a hydrogen atom, an acetoxy group or a lower alkoxy group by treatment with a mixture of trifluoracetic anhydride and trifluoracetic acid and hydrolyzation of the acethoxy groups with sodium methylate,

(x) oxidation of the 1-hydroxyethylene group of the resultant I compound of general formula XIII wherein R has the meaning defined above with silver carbonate and oxidative demethylation of the resulting compound with aluminum trichloride in nitrobence and

(xi) protection of the 13-keto group of the resulting compound i5 of the general formula XIV by treatment with ethylene glycol,

bromination of the resulting C-7 compound by treatment in the presence of 2-2 '-azo-bis- (isobutyronitrile) with bromine or N-bromosuccinimide, and hydrolization of the 7-bromine and 13-ketal groups.

NNHTs

11

HjCOO

h3cooc

OCH

OCH.

n OCHj 0

IX

5

661 922

OCH

OCH

OH

OCH

THE

OH

OCH

OH

OCH

R

OCH

OCOCH

COCH

OCH

OCH

OH

CH

OH

OH

OH

THE

The starting products for the process according to the invention are known. 2-Bromo-l, 4,5-trimethoxynaphthalene (VII,

R = OCH3) is described by R.L. Haman, R.B. Barber and H. Rapo-port, J. Org. Chem., 44, 2153 (1979). The copulation reaction between compounds VII and VI proceeds selectively in high yields to give the key intermediate IX. The organometallic compound acts only on the carbonyl group of the methyl ester and not on that of the lactone.

The passage (xi) can be carried out according to the known method described by C.M. Wong et al., Can. J. Chem., 51, 446 (1973), which consists of bromination with bromine in the presence of 2,2 '-azo-bis- (isobutyronitrile) followed by hydrolysis of the 7-bromine derivative and removal of the ketal group by acid treatment or alternatively by bromination with N-bromo-succinimide in the presence of 2,2 '-azo-bis (isobutyronitrile), by irradiation, treatment with silver acetate, hydrolysis of the ketal by acid treatment and finally hydrolysis of the acetate with sodium methoxide.

Optical resolution of compound IX can be accomplished by conventional conversion methods to diaste-rheoisomer derivatives using a chiral resolving agent. The resolution now leads to the compounds (+) -4-demethoxy-6-deoxy-4 - (R-substituted) -ununomycinones I. I 6-deoxyanthracyclinons I, with the exception of those in which R represents a hydrogen atom , are new and are included in the scope of the invention. 4-Demethoxy-6-deoxidaunomycinone, prepared by a different process has already been described in the British patent No. 2 100 257 of the applicant. The present process is more effective and moreover possible to carry it out on an industrial scale with better results than those described in the previous process.

The following examples illustrate the invention.

Example 1

Dimethyl l, 2,3,6-tetrahydro-4-acetyl-phthalate (III)

10 g of dimethyl 1,2,3,6-tetrahydro-phthalate (II) are treated at -5 ° C with 25 ml of acetic anhydride in the presence of 9 ml of tin te-trachloride. The reaction mixture is poured into ice water and then extracted with diethyl ether. The organic phase is washed with a saturated aqueous sodium bicarbonate solution and then with water and is finally evaporated to dryness under vacuum. The oil obtained is dissolved in benzene, treated with a methanolic solution of hydrochloric acid. The solution is evaporated to dryness and the residue is purified by chromatography on a silica gel column to obtain 9 g of the title product in a yield greater than 75%.

Mass spectrum: m / z 240 (M +)

IR (K Br): 1720 cm ~ '(C = 0 of ester); 1660 was "1 (C = 0 of a, ß unsaturated ketone)

PMR (CDCI3): inter alia Ô 2.33 (s, COCH3), 3.70 (s,

-COOCH3) and 6.91 (m, HC = C)

Example 2

l, 2-Di- (methoxycarbonyl) -4-ethylidene-cyclohexane (V)

17 g of dimethyl 1, 2,3,6-tetrahydro-4-acetyl-phthalate, prepared according to what described in example 1, is heated to reflux in anhydrous methanol with 14.6 g of tosylhydrazine. After removing the solvent 24 g of dimethyl 1, 2,3,6-tetrahydro-4- (1-tosyl-hydrazono-ethyl) -phthalate (IV) crystallizes from water: m.p. 162 ° -163 ° C m / z 408 (M +).

This compound is dissolved in chloroform and treated at 0 ° C with 14 ml of borane catechol. Sodium acetate is added to the reaction mixture which is then heated to reflux. After washing with water, the solvent is evaporated and the residue is purified by chromatography on a silica gel column and 10 g of the title compound are obtained (80% yield): m / z 226 (M +);

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PMR (CDCI3): inter alia 6 1.6 (d, J = 8Hz, ÇH3-CH =), 5.3 (q, J = 8Hz, CH3-CH =).

Example 3

2-Methoxycarbonyl-5- (2-methyldioxolan-2-yl) -6-oxa-bicycle [3,2, lJ-octan-7-one (VI)

8 g of 1,2-di- (methoxycarbonyl) -4-ethylidene-cyclohexane, prepared as described in Example 2, is dissolved in aqueous acetone containing 4.8 ml of acetic acid. An aqueous solution of potassium permanganate is added and the mixture is left for 60 minutes at room temperature. The oxidizing excess is then destroyed and the reaction mixture diluted with water is extracted with ethyl acetate. The organic phase is evaporated to dryness under vacuum, washed with water and dried over anhydrous sodium sulphate. The residue (9 g) is dissolved in benzene and heated to reflux for 60 minutes in the presence of a catalytic amount of P-toluene sulfonic acid. 4 ml of ethylene glycol are added and the reaction mixture is refluxed for a period of 2 hours. After removing the solvent, the residue is purified by chromatography on a silica gel column using a toluene: acetone (15: 1 by volume) mixture as eluent.

3 g of the title product are obtained (yield of 33%): m.p. 69 ° -71 ° C; m / z 271 (MH +).

IR (KBr): 1790 cm-1 (C = 0 5-member lactone ring) 1735 cm — 1 (C = 0 ester); 1720 cm ~ 1 (C = 0 ketone) PMR (CDCI3): inter alia 1.25 (s, CH3), 3.65 (s, COOÇH3), and 3.9 (s, -O-ÇH2-ÇH2-O -).

Example 4

2- (l, 4,5-trimethoxy-3-naphthylcarbonyl) -5- (2-methyl-dioxolan-2-yl) - 6-oxa-bicycle [3,2, l Jottan-7-one (IX, R = OCH3)

7 ml of a 1.65 m hexane solution of n-butyllithium are dissolved in 30 ml of anhydrous tetrahydrofuran. A solution of 3,3 g of l, 4,5-trimethoxy-3 - bromo-naphthalene (VI, R = OCH3) in 30 ml of anhydrous tetrahydrofuran is added to the solution at -78 ° C.

2,5 g of 2-methoxy-carbonyl-5- (2-methyl-dioxolan-2-yl) -6-oxa - bicyclo [3,2, l] -octane-7-one, prepared and described in Example 3, are added in 50 ml of anhydrous tetrahydrofuran and added to the reaction mixture. This mixture is kept for one hour at -78 ° C and then acetic acid is added. The solvent is removed under vacuum. The residue is purified on a silica gel column and 3 g of the title compound (73% yield), m / z 456 (M +) are obtained.

IR (KBr): 1775 cm ~ 1 (C = 0 lactone with 5-membered ring)

1680 cm-1 (C = 0 benzyl ketone)

PMR (CDC13): inter alia 1.3 (s, CH3), 3.75 (s, OCH3),

3.95-4.05 (m, two OÇH3 and -O-Œ2-ÇH2-O-),

6.8 (s, aromatic CH) and 6.8-8.1 (m, three H).

Example 5

l- (l, 4,5-trimethoxy-3-naphthylmethyl-2-benzyloxycarbonyl-4- (l - hydroxyethyl) -4-hydroxy-cyclohexane (XI, R - OCH3)

1.6 g of 2- (1, 4,5-trimethoxy-2-naphthyl-carbonsI) -5- (2-methyl-dioxyIan-2-yl) -6-bones-bicycle are dissolved in methanol [3,2 , the octane-7-one prepared as described in Example 4 and treated at room temperature for 1 hour with an IN solution of hydrochloric acid in anhydrous methanol. After eliminating the solvent by evaporation, 1.5 g of l- (1, 4,5-trimethoxy-3-naphthylcarbonyl) -2-methoxycarbonyl-4-ace-til-4-hydroxy-cyclohexane are obtained in almost quantitative yields ( X, R = COH3).

m / z 444 (M +);

IR (film): 3460 cm -1 (OH), 1730 cm "1 (C = 0 ester), 1710 cm ~ 1 (C = 0 ketone) and 1665 cm-1 (C = 0 benzyl ketone).

PMR (CDC13): inter alia 2.3 (s, ÇH3CO), 3.75-4.05 (s, four OCHi). 6.8 (s, aromatic H) and 6.85-8.0 (m, three aromatic H).

1.5 g of this compound are dissolved in 15 ml of trifluoracetic acid heated to reflux with 1.4 ml of a pyridine-borane complex. After removing the solvent, the residue is treated with a 10% aqueous solution of sodium hydrate. After a mild acidification, the free acid is extracted with ethyl acetate. The solvent is removed by evaporation and the residue is directly treated with an ethereal solution of phenyldiazomethane to obtain the title product. This is then purified by chromatography:

m / z 508 (M +);

PMR (CDC13): inter alia 1.25 (d, CH3-CH), 3.70-3.95 (s, three OCH3), 5.15 (d, CH? Ph) and 6.4-8.1 (m, nine aromatic H).

Example 6

1,2,3,4,4a, 5,12,12a-Octahydro-2- (l-hydroxyethyl) -2-hydroxy-6,7,11 - trimethoxy-12-oxonnaftacene (XIII, R = OCH3)

0.48 g of 1- (1, 4,5-trimethoxy-3-naphthylmethyl) -2-benzyloxycarbo-nyl-4- (1-hydroxyethyl) -4-hydroxy-cyclohexane, prepared as described in Example 5, are treated with acetic anhydride and pyridine in the presence of 4-dimethylamino-pyridine. After one night at room temperature the reaction mixture is poured into ice water and poured with ethyl acetate. The organic layer is washed with water and concentrated. The crude product is dissolved in methanol and heated to reflux with cyclohexene in the presence of 10% by weight of palladium on coal. The catalyst is then filtered and the solution concentrated in a small volume and treated at 0 ° C for 60 minutes with trifluoroacetic anhydride and trifluoroacetic acid. The solution is then diluted with ethyl acetate, washed with a saturated aqueous sodium bicarbonate solution and with water, dried and concentrated to dryness under vacuum. The residue is dissolved in methanol in the presence of a catalytic amount of methylated sodium. We proceed with the known methods and by purification by chromatography 0.18 g of the title product are obtained (yield 49%):

m / z 400 (M + -);

IR (KBr): 3450 cm "1 (OH), 1675 cm" 1 (C = 0 benzyl ketone;

PMR (CDC13): inter alia 8 1.2 (d, CH3-CH), 3.7-3.9 (s, OÇH3) and 6.4-8.0 (m, three aromatic H).

Example 7

1,2,3,4,4a, 5,12,12a-octahydro-2-acetyl-2-hydroxy-6,7,11 - trimethoxy-12-oxo-tetracene

0.8 g of silver carbonate are added to a benzene solution of 0.09 g of 1,2,3,4,5a, 5,12,12a-octahydro-2- (1 - hydroxyethyl) -2- hydroxy-6,7,1 l-trimethoxy-12-oxo-naphtacene, prepared as described in example 6 and the mixture is heated to reflux. After removing the solid by filtration and evaporating the solvent under vacuum, 0.08 g of the title compound (90% yield) are obtained.

IR (KBr): 3360 cm "1 (OH), 1705 cm" 1 (C = 0 ketone),

1680 cm-1 (C = 0, benzyl ketone)

PMR (CDCI3): inter alia 8 2.2 (s, CH3CO), 3.65-3.90 (s, three OCH3).

Example 8

6,7-Dexoxycarminomycinone (XIV, R = OH)

0,06 of 1,2,3,4,4a, 5,12,12a-octahydro-2-acetyl-2-hydroxy-6,7,11 - trimethoxy-12-oxonaftacene, prepared as described in example 7 , are dissolved in nitrobenzene and treated with 0.12 g of aluminum trichloride. The mixture is kept at 70 ° C until the starting product is no longer traceable. There

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661 922

reaction mixture is poured into an aqueous saturated salic acid solution and then extracted with ethyl acetate. The organic phase is separated, washed with water, dried and evaporated to dryness. The purified residue on a silica gel column gives the pure compound 6,7-dexoxycarminomycinone, yield of 40%:

m / z 352 (M +);

IR (KBr): 3420 cm (OH), 1705 cm "1 (C = 0 ketone) e

1625 cm-1 (C = 0 chelated quinone).

PMR (CDCI3): inter alia 1.7-2.2 (m, CH2), 2.3 (s, CH3CO), 2.8-3.2 (m, two benzyl CH2), 7.0-7, 9 (m, four aromatic H), 12.6 (s phenolic OH) and 12.9 (s, phenolic OH).

Example 9

6-Deoxycarminomycinone (I: R = OH)

A benzene solution of 6,7-dideoxydicarminomycinone, prepared as described in Example 8, is heated to reflux for 4 hours with 1.2 ml of ethylene glycol in the presence of a catalytic amount of p-toluene sulfonic acid, and the corresponding is obtained 13-ketal derivative. This compound is dissolved in carbon tetrachloride and treated with 2 ml of a solution of 3.2 g of bromine in 32 ml of carbon tetrachloride at 45 ° C for 6 hours in the presence of 2.2 '-azo-bis (isobutyrronitrile ). The reaction mixture cooled with aqueous sodium hydrate IN is extracted and the pH of the colored aqueous phase is adjusted to 8.5 and extracted with chloroform. The organic extracts evaporated to dryness give the compound 6-deoxy-13-ketal-carminomycinone. This is dissolved in acetone containing hydrochloric acid (300 ml of a 0.25 N solution) and the room temperature is kept for 3 hours in order to hydrolyze the ketal group.

The desired 6-deoxycarminomycinone is obtained in this way.

Alternative method

A solution of 50 mg (0.125 mmol of the 13-ketal derivative of 6,7-didooxycarminomics-none in 20 ml of carbon tetrachloride containing 0.14 mmol of N-bromo-succinimide and 0.06) is heated to reflux for 25 minutes mmol of 2,2 '-azo-bis (isobutyrro-nitrile). The residue obtained after evaporating the solvent under vacuum is dissolved in glacial acetic acid and treated with 80 mg of silver acetate. The mixture is stirred at room temperature for 5 hours. The solvent is eliminated by evaporation and the residue is dissolved in ethyl acetate and filtered. The filtrate is washed with a saturated aqueous sodium bicarbonate solution and then with water, dried and concentrated. The residue is dissolved in aqueous acetic acid. (90% by volume) at 0 ° C and kept under stirring for 90 minutes.

After removing the solvent, the residue is dissolved in methanol, sodium methoxide is added and the mixture is kept under stirring for 90 minutes. After neutralization, extraction and washing with water, the residue is purified by chromatography with methylene chloride: acetone (16: 1 by volume). The desired 6-deoxycarminomycinone is obtained with a yield of 34%.

m / z 368 (M +), m.p. 211-213 ° C, TLC on a Kieselgel layer (Merck F254) using toluene as an eluent: 4: 1 acetone by volume, Rf = 0.3.

PMR (200 MHz, CDCI3): 2.1-2.3 (m, 2H, H-8), 2.3 (s. 3H, -COCH3), 2.7-3.1 (q, 2H, H -10), 4.1 (d, IH, OH-7), 4.4 (s, IH, OH-9), 4.8 (d, IH, H-7), 7.3 (d, IH , H-3), 7.7 (t, IH, H-2), 7.8 (d, IH, Hl), 8.1 (s, IH, H-6), 12.8 (s, IH , OH-4), 13.2 (s, IH, OH-11).

Example 10

2- (1, 4-Dimethoxy-3-naphthylcarbonyl) -5- (2methyl-dioxolan-2-yl) -6 - bicyclic bones [3,2, l] octan-7-one (IX, R = H )

Following the method described in Example 4, a solution of 3,2 g of 1,4-dimethoxy-3-bromo-naphthalene in anhydrous tetrahydrofuran is treated at -78 ° C with n-butyllithium and then added to a solution in anhydrous tetrahydrofuran of 2.7 g of the compound prepared in Example 3. After a purification on a silica gel column, 2.8 g of the title compound are obtained (65% yield).

m / z 426 (M +);

IR (film): 1780 cm — 1 (C = 0, 5-member lactone ring),

1670 cm-1 (C = 0, benzyl ketone);

PMR (CDCI3): inter alia: 5 1.4 (s, CH3), 3.85 (s, two OCH3), 3.9 (s, -O-CH2-CH2-O-), 6.9 (s , Aromatic H) and 7.4-8.4 (aromatic m 4H).

Example 11

l- (l, 4-dimethoxy-3-naphthylmethyl) -2-benzyloxycarbonyl-4- (l-hydroxy-ethyl) -4-hydroxy-cyclohexane (XI, R = H)

Operating as described in Example 5, the 2- (1,4-dimethoxy-3-naphthylcarbonyl) -5- (2-methyl-dioxolan-2-yl) -6-bone-bi-cycle is treated [3, 2, 1] octane-7-one, prepared as described in the example

10, with a solution of hydrochloric acid in methanol to obtain 1- (1,4-dimethoxy-3-naphthylcarbonyl) -2-methoxycarbonyl-4 - acetyl-4-hydroxy-cyclohexane (X, R = H) in almost yields quantitative, m / z 414 (M +);

IR (film): 3460 cm-1 (OH), 1730 —1 (C = 0 ester), 1710 cnr ~ '

(C = 0 ketone) and 1670 cm-1 (C = 0, benzyl ketone). PMR (CDC13): inter alia: 2.3 (s, CH3CO), 2.9-3.6 (m, two H), 3.7-3.9 (s, three OÇH3), 6.9 (s , H aromatic) and 7.4-8.4 (m, four aromatic H).

1 g of this compound by reduction with the pyridine-borane complex, basic treatment and finally esterification with phenildiazomethane is transformed into the title compound (0.7 g yields of 63%).

m / z 478 (M +);

IR (film): 3450 cm-1 (OH), 1725 cm "1 (C = 0, ester). PMR (CDCI3): inter alia 5 1.3 (d, J = 4Hz, ÇH3-CH), 3, 85-3.9 (s, two OCH3), 5.1 (s, CH2-benzyl), 6.6 (s, aromatic H) and 7.2-8.4 (m, nine aromatic H).

Example 12

1,2,3,4,4a, 5,12,12a-Octahydro-2- (l-hydroxyethyl) -2-hydroxy-6,11 - dimethoxy-12-oxo-naphtacene (XIII, R = H)

By operating as described in Example 6, 0.44 g of l- (1,4-dimethoxy-3-naphthylmethyl) -2-benzyloxycarbonyl-4- (1-hydroxy-ethyl) -4-hydroxy-cyclohexane are treated, prepared as described in the example

11, with acetic anhydride in the presence of 4-dimethylamino-pyridi-na and pyridine. The corresponding acetate is treated with cyclohexane in the presence of palladium on coal in 10% by weight to remove the benzyl group. The acid is cyclized by treatment with a mixture of trifluoracetic anhydride and trifluoroacetic acid at 0 ° C. Finally, the O-protective acetyl groups are eliminated by treatment with sodium methylate to obtain, after purification by silica gel chromatography, 0.225 g of the title compound (66% yield).

IR (film): 3450 cm-1 (OH), 1675 cm-1 (C = 0, benzyl ketone).

PMR (CDCI3): inter alia 1.3 (d, J = 4Hz, ÇH3-CH), 1.6-3.5 (m, 3H), 3.85 (s, OCH3), 3.90 (s, OCH3), 7.2-8.4 (m, four aromatic H).

Example 13

l, 2,3,4,4a, 5,12,12a-Octahydro-2-acetyl-2-hydroxy-6,11 -dimethoxy - 12-oxo-naphtacene

0.1 g of l, 2,3,4,4a, 5,12,12a-octahydro-2- (l-hydroxyethyl) -2-hydros-

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si-6, 11-dimethoxy-12-oxo-naphtacene, prepared as described in Example 12, in benzene, is treated with 1 g of silver carbonate at the refluxing temperature. After filtration, the inorganic solids are eliminated and the solvent is then eliminated; 0.1 g of the title compound is obtained.

IR (film): 3460 cm (OH), 1710 cm "1 (C = 0 ketone), 1680 cm1— (C = 0 benzyl ketone)

PMR (CDCI3): inter alia S 2.4 (s, CH3CO), 3.85 (s, OCH3), 3.90 (s, OCH3), 7.2-8.4 (m, four aromatic H).

Example 14

a-Demethoxy-6,7-dideoxidaunomycinone (XIV, R = H) Operating as described in example 8, a solution of 0.1 g of 1,2,3,4,4a, 5,12,12a is treated Octahydro-2-acetyl-2-5 -hydroxy-6, 11-dimethoxy-12-oxo-naphthacene, prepared as described in Example 13, in 3 ml of nitrobenzene with 0.25 g of aluminum trichloride and held for all night at room temperature. Chromatography is carried out on a silica gel column and 0.055 g (63% yield) of the title compound is obtained. 10 m.p. 203-204 ° C.

v

Claims (4)

661 922 2. 6-Deoxyanthracyclinones prepared according to the process of claim 1, having the general formula I: OH CH OH OH wherein R represents a hydroxyl group or a lower alkoxy group. 2 CLAIMS 1. Process for the preparation of 6-deoxyanthracycles-noni having the general formula I: OH CH OH OH wherein R represents a hydrogen atom, a hydroxyl group or a lower alkoxy group, characterized in that a di-methyl 1,2,3,6-tetrahydro-phthalate of formula II: by treatment with acetic anhydride in the presence of tin tetrachloride, and subsequently by treatment with a weak base or a weak acid it is transformed into dimethyl 1,2,3,6-tetrahydro-4-acetyl-phthalate III: OR CH which, when reacted with tosylhydrazine gives the corresponding dimethyl 1,1,3,6-tetrahydro-4- (1-tosylhydrazono-ethyl) -phthalate IV: CB and by reducing compound IV with catechol borane and subsequently modifying the double bond from an endocyclic position to an exocyclic in the presence of sodium acetate, 1,2-di- (methoxycarbonyl) -4-ethyliden-cyclohexane V is obtained: from which, after an oxidative treatment with potassium permanganate, the corresponding a-hydroxy ketone is obtained and subsequently reacted with ethylene glycol in the presence of a catalytic quantity of p-toluenesulfonic acid to give 2-methoxy-5- [2-methyl -diossolan-2-yl] -6-bones-bicycle [3,2, l] -ottan-7 - one VI: CH which dissolved in anhydrous tetrahydrofuran is condensed at a temperature of -78 ° C and for 1 hour, with a derivative alkylithium of formula VIII: OCH., Vili OCH where R has the above meaning, to obtain lactone IX: OCH CH OCH and the lactone ring of the compound is opened by methanolysis and at the same time the protective keto group of the dioxolane is eliminated by acid treatment to obtain the compound of formula X: OCH OCH OH iCH 5 10 15 20 25 30 35 40 45 50 55 60 65 3. 4-Demethyl-6-deoxy-daunomycinone as a compound according to claim 2, having the general formula I wherein R = OH. 3 661 922 wherein R has the above meaning, the keto group of compound X is reduced by treatment with a pyridine-borane complex in the presence of typhluoracetic acid and the methoxycarbonyl group is converted into a benzyloxycarbonyl group by treatment with phenyldiazomethane to obtain the compound of formula XI : OH OCH OH R OCH the hydroxyl groups are esterified and the benzyloxycarbonyl group of compound XI is deesterified, wherein R has the above meaning by treatment with acetic anhydride in pyridine in the presence of 4-dimethylamino-pyridine followed by heating to reflux with cyclohexene in the presence of palladium on coal to give the compound of formula XII: OCH OCOCH OH COCH OCH wherein R 'represents a hydrogen, an acetoxy group or a lower alkoxy group, which undergoes cyclization by treatment with a mixture of trifluoracetic anhydride and trifluoracetic acid and by subsequent hydrolysis of the acetoxy groups with methylated sodium, compound XIII is obtained : OH OCH CU OH iCH wherein R has the above meaning from which, after an oxidative treatment of the 1-hydroxyethyl group with silver carbonate and demethylation of the resulting compound with aluminum trichloride in nitrobenzene, the compound of formula XIV is obtained: OH OH from which, after protection of the 13-keto group by treatment with ethylene glycol, bromination of the resulting compound in C-7 with bromine in the presence of 2,2 '-azo-bis (isobutyronitrile) followed by hydrolysis of the 7-bromine derivative and elimination of the ketal group by acid treatment, or alternatively by bromination with N-bromine succinimide in the presence of 2-2 '-azo-bis (isobutyronitrile), by irradiation, treatment with silver acetate, hydrolysis of the ketal by acid treatment and finally hydrolysis of the acetate with sodium methoxide the desired compounds of formula I are obtained. 4. 6-Deoxy-daounomycinone as a compound according to claim 2, having the general formula I wherein R = OCH3.